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JP6975609B2 - Hydrophilicity retaining substrate, measuring device, device and hydrophilicity retention method - Google Patents

Hydrophilicity retaining substrate, measuring device, device and hydrophilicity retention method Download PDF

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JP6975609B2
JP6975609B2 JP2017202700A JP2017202700A JP6975609B2 JP 6975609 B2 JP6975609 B2 JP 6975609B2 JP 2017202700 A JP2017202700 A JP 2017202700A JP 2017202700 A JP2017202700 A JP 2017202700A JP 6975609 B2 JP6975609 B2 JP 6975609B2
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崇秀 横井
佑介 後藤
一真 松井
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Description

本開示は、生体分子または無機分子の計測や反応等に用いる親水性保持基材、計測装置、デバイスおよび親水性保持方法に関する。 The present disclosure relates to a hydrophilicity-retaining substrate, a measuring device, a device and a hydrophilicity-retaining method used for measurement and reaction of biomolecules or inorganic molecules.

溶液中に存在する分子を検出する方法として、微細な検出部(厚さがnmオーダーの薄膜)を有するナノデバイスを用いる方法が注目されている。ナノデバイスは、対象分子をマーカーによって標識することなく溶液中に存在する分子を計測可能である。 As a method for detecting molecules existing in a solution, a method using a nanodevice having a fine detection part (thin film having a thickness on the order of nm) is attracting attention. Nanodevices can measure molecules present in solution without labeling the molecule of interest with a marker.

上下の溶液槽を仕切る薄膜にナノメータサイズの細孔(ナノポア)を施したナノデバイスは、ナノポアを通過する分子の種類および数を電流値にて検出が可能である。この原理を用いた分子の計測事例として、低分子化合物、DNA等の核酸分子およびタンパク質の検出が、非特許文献1において報告されており、今後利用の拡大が見込まれる。 Nanodevices with nanometer-sized pores (nanopores) on the thin film that separates the upper and lower solution tanks can detect the type and number of molecules that pass through the nanopores by current value. As an example of measurement of molecules using this principle, detection of nucleic acid molecules and proteins such as small molecule compounds and DNA has been reported in Non-Patent Document 1, and its use is expected to expand in the future.

他の微細加工デバイスとして、ナノサイズの間隙を電極対として利用するナノギャップデバイスが非特許文献2に開示されている。また、非特許文献3には、導電性または半導電性のナノファイバーを利用するナノワイヤーデバイスが開示されている。 As another microfabrication device, a nanogap device that utilizes a nano-sized gap as an electrode pair is disclosed in Non-Patent Document 2. Further, Non-Patent Document 3 discloses a nanowire device using conductive or semi-conductive nanofibers.

これらナノデバイスは半導体加工に用いられる微細加工技術によって作製されるため、シリコンを含む素材で形成されている。シリコン素材は高純度化可能であり、微細加工性が高いといった大きな利点がある。例えば、前述のナノポアは、シリコン素材の薄膜の両面を導電性の溶液で濡らして両側から電圧を印加し、絶縁破壊を生じさせることによって形成する。しかし、シリコンを含む素材は疎水性であるため、シリコン素材からナノデバイスを作製して溶液中の分子検出に供するには、ナノポアを形成する前にシリコン素材表面の親水化処理が必要となる。 Since these nanodevices are manufactured by the microfabrication technology used for semiconductor processing, they are made of a material containing silicon. Silicone materials can be highly purified and have great advantages such as high microfabrication. For example, the above-mentioned nanopores are formed by wetting both sides of a thin film of a silicon material with a conductive solution and applying a voltage from both sides to cause dielectric breakdown. However, since the material containing silicon is hydrophobic, in order to prepare a nanodevice from the silicon material and use it for molecular detection in a solution, it is necessary to hydrophilize the surface of the silicon material before forming nanopores.

シリコン素材表面を親水化する技術として親水性ポリマーを固定する技術が利用されている。しかしながら、親水性ポリマーを基板表面に結合する技術は、表面構造が変化するため微細な構造によって分子を検出するナノデバイスには不適合である。そのため、ナノデバイスの親水化処理では表面構造に変化を与えない手法であるピラニア洗浄またはプラズマ処理が用いられている。 As a technique for making the surface of a silicon material hydrophilic, a technique for fixing a hydrophilic polymer is used. However, the technique of binding a hydrophilic polymer to the surface of a substrate is not suitable for nanodevices that detect molecules by a fine structure because the surface structure changes. Therefore, in the hydrophilization treatment of nanodevices, piranha cleaning or plasma treatment, which is a method that does not change the surface structure, is used.

Haque, F., et al., Solid-State and Biological Nanopore for Real-Time Sensing of Single Chemical and Sequencing of DNA, Nano Today. 8(1), p. 56-74 (2013).Haque, F., et al., Solid-State and Biological Nanopore for Real-Time Sensing of Single Chemical and Sequencing of DNA, Nano Today. 8 (1), p. 56-74 (2013). Chen, X., et al., Electrical nanogap devices for biosensing, materialstoday. 13(11), p. 28-41 (2010).Chen, X., et al., Electrical nanogap devices for biosensing, materialstoday. 13 (11), p. 28-41 (2010). Patolsky, F., et al., Nanowire sensors for medicine and the life sciences. Nanomedicine 1(1), p. 51-65 (2006).Patolsky, F., et al., Nanowire sensors for medicine and the life sciences. Nanomedicine 1 (1), p. 51-65 (2006).

ところで、上記のピラニア洗浄またはプラズマ処理によって得られた表面親水化の効果は、経時的に低下する。そのため、基板表面の親水化処理はシリコン薄膜に溶液を接触させる直前に行うことが望ましい。以下に説明するように、このことはナノデバイスによる分子計測技術を普及させるにあたっての障害となる。 By the way, the effect of surface hydrophilization obtained by the above-mentioned piranha washing or plasma treatment decreases with time. Therefore, it is desirable that the hydrophilic treatment of the substrate surface is performed immediately before the solution is brought into contact with the silicon thin film. As will be explained below, this is an obstacle to the spread of molecular measurement technology using nanodevices.

(Case1)ナノデバイスの使用者がナノデバイスを製造する場合
親水化処理を使用者が行う場合、プラズマ照射装置を保有するか、ピラニア溶液を取り扱う必要がある。しかしながら、プラズマ照射装置は高価であり使用者が保有するには負担が大きい。また、硫酸と過酸化水素水との混合液体であるピラニア溶液は非常に危険であるため、使用者に本処理を委託することは困難である。
(Case1) When the user of the nanodevice manufactures the nanodevice When the user performs the hydrophilization treatment, it is necessary to have a plasma irradiation device or handle a piranha solution. However, the plasma irradiation device is expensive and burdensome for the user to own. In addition, since the piranha solution, which is a mixed liquid of sulfuric acid and hydrogen peroxide solution, is extremely dangerous, it is difficult to outsource this treatment to the user.

(Case2)ナノデバイスの製造者と使用者が一致しない場合
親水化処理を製造者が行う場合、親水化処理の効果が低下する前に薄膜を備える計測チップに溶液を添加する必要がある。しかしながら、薄膜の親水性が劣化する前に溶液添加を達成するには、ウェハーからの薄膜のピックアップ、溶液槽への組込といった一連の工程を迅速に行うことが要求される。つまり、計測チップを一度に大量に生産するには時間的制約が存在する。また、計測チップへの溶液添加を行うためには、溶液添加装置に加えて添加溶液の蒸発を防ぐために溶液注入口をシールする技術が要求されることも負担を大きくする。
(Case2) When the manufacturer and the user of the nanodevice do not match When the hydrophilization treatment is performed by the manufacturer, it is necessary to add the solution to the measuring chip provided with the thin film before the effect of the hydrophilization treatment is reduced. However, in order to achieve solution addition before the hydrophilicity of the thin film deteriorates, it is required to quickly perform a series of steps such as picking up the thin film from the wafer and incorporating it into the solution tank. That is, there is a time constraint for mass-producing measurement chips at one time. Further, in order to add the solution to the measuring chip, a technique of sealing the solution injection port in order to prevent evaporation of the added solution is required in addition to the solution adding device, which also increases the burden.

上述したように基板表面の親水化処理の実行者が使用者であっても、製造者であっても、薄膜を組み込んだ計測チップの作製と利用は容易でない。この問題は親水化処理を施した薄膜の親水性が経時的に低下することに起因しているため、基板表面の親水性を保持する技術によって解決可能である。 As described above, it is not easy to manufacture and use a measuring chip incorporating a thin film, regardless of whether the person performing the hydrophilization treatment on the substrate surface is the user or the manufacturer. Since this problem is caused by the decrease in hydrophilicity of the hydrophilized thin film over time, it can be solved by a technique for maintaining the hydrophilicity of the substrate surface.

また、薄膜の微細な構造やその計測特性を維持するためには、用いられる親水性保持技術は薄膜に化学的または物理的な改変を伴わない技術であることが要求される。さらには、基板表面に施す親水性保持処理は本来の目的である分子計測に与える影響が少ないことが望ましい。また、親水性保持技術を適用した薄膜を組み込んだ計測ユニットが常温常圧で保管可能であれば、製造、輸送、販売といった製造から使用者の消費にいたるまでの過程において脱気密封や冷蔵等の設備が不要となるため、当該技術の価値がさらに向上する。 Further, in order to maintain the fine structure of the thin film and its measurement characteristics, the hydrophilicity retention technique used is required to be a technique that does not involve chemical or physical modification of the thin film. Furthermore, it is desirable that the hydrophilicity-retaining treatment applied to the surface of the substrate has little effect on the molecular measurement, which is the original purpose. In addition, if the measuring unit incorporating the thin film to which the hydrophilicity retention technology is applied can be stored at normal temperature and pressure, degassing, sealing, refrigerating, etc. in the process from manufacturing to user consumption such as manufacturing, transportation, and sales. The value of the technology is further improved because the equipment of the above is not required.

本開示は、以上のことを鑑み、基板の構造や特性を変化させずに、基板表面の親水性を長期に亘って簡単な管理で維持できる技術を提供する。 In view of the above, the present disclosure provides a technique capable of maintaining the hydrophilicity of the substrate surface for a long period of time with simple management without changing the structure and characteristics of the substrate.

上記課題を解決するために、本開示は、親水性の面を有する親水性部材と、前記面上に形成された、可溶性物質を含む保護層と、を有する親水性保持基材を提供する。 In order to solve the above problems, the present disclosure provides a hydrophilic retaining base material having a hydrophilic member having a hydrophilic surface and a protective layer containing a soluble substance formed on the surface.

さらに、本開示は、前記親水性保持基材を含む計測装置を提供する。 Further, the present disclosure provides a measuring device including the hydrophilicity-retaining substrate.

また、本開示は、前記親水性保持基材を有するデバイスであって、前記親水性部材は、厚さが1μm以下の薄膜形状かつ絶縁性であり、前記親水性部材が有する二面のうち少なくとも一方の表面に前記可溶性物質を含む保護層が形成されているデバイスを提供する。 Further, the present disclosure is a device having the hydrophilicity-retaining substrate, wherein the hydrophilic member has a thin film shape and an insulating property having a thickness of 1 μm or less, and at least one of the two surfaces of the hydrophilic member. Provided is a device in which a protective layer containing the soluble substance is formed on one surface.

さらにまた、本開示は、基板の表面を親水化処理する工程と、親水化処理後の前記基板表面に可溶性物質を含む溶液を塗布する工程と、塗布した前記溶液を乾燥させる工程と、を有する基板表面の親水性保持方法を提供する。 Furthermore, the present disclosure includes a step of hydrophilizing the surface of the substrate, a step of applying a solution containing a soluble substance to the surface of the substrate after the hydrophilic treatment, and a step of drying the applied solution. A method for maintaining hydrophilicity on a substrate surface is provided.

本開示は、基板の構造や特性を変化させずに、基板表面の親水性を長期に亘って簡単な管理で維持できる技術を提供する。上記した以外の課題、構成および効果は、以下の実施形態の説明により明らかにされる。 The present disclosure provides a technique capable of maintaining the hydrophilicity of a substrate surface for a long period of time with simple management without changing the structure and characteristics of the substrate. Issues, configurations and effects other than those described above will be clarified by the description of the following embodiments.

ナノデバイスによって分子計測をする際の処理のフローである。This is the flow of processing when measuring molecules with nanodevices. 親水化処理が施された基板表面に純水を垂らした際の親水性または撥水性を示す図である。It is a figure which shows the hydrophilicity or water repellency when pure water is dropped on the surface of the substrate which has been subjected to the hydrophilic treatment. 基板表面に垂らした純水の接触角の経時的変化を示す図である。It is a figure which shows the time-dependent change of the contact angle of pure water dripping on the substrate surface. ナノデバイスの構造を示す図である。It is a figure which shows the structure of a nanodevice. 本開示の親水性保持方法を適用したナノデバイスと適用しなかったナノデバイスとでリーク電流を測定した結果を比較した図である。It is a figure which compared the result of having measured the leakage current between the nanodevice to which the hydrophilicity retention method of this disclosure was applied, and the nanodevice to which it was not applied. 本開示の親水性保持方法を適用したナノデバイスによって分子計測をする際の処理のフローである。It is a flow of the process at the time of molecular measurement by the nanodevice to which the hydrophilicity retention method of this disclosure is applied. ナノデバイスに形成された保護層を除去して分子計測を実施する様子が示された図である。It is a figure which showed the state of performing the molecular measurement by removing the protective layer formed on the nanodevice. 本開示の親水性保持方法を適用したナノデバイスで観察された電圧印加累積時間とイオン電流との関係を示す図である。It is a figure which shows the relationship between the cumulative voltage application time observed in the nanodevice to which the hydrophilicity retention method of this disclosure was applied, and an ionic current. ナノデバイスの初期欠陥の有無を示す図である。It is a figure which shows the presence or absence of the initial defect of a nanodevice. ナノデバイスの初期欠陥の有無を示す図である。It is a figure which shows the presence or absence of the initial defect of a nanodevice. 分子計測の測定結果の例を示す図である。It is a figure which shows the example of the measurement result of a molecular measurement.

本実施の形態を説明するための全図において同一機能を有するものには同一の符号を付すようにし、その繰り返しの説明は可能な限り省略するようにしている。また、本開示は以下に示す実施の形態の記載内容に限定して解釈されるものではない。本開示の思想ないし趣旨から逸脱しない範囲で、その具体的構成を変更し得ることは当業者であれば容易に理解される。 In all the drawings for explaining the present embodiment, the same reference numerals are given to those having the same function, and the repeated description thereof is omitted as much as possible. In addition, the present disclosure is not construed as being limited to the description of the embodiments shown below. It is easily understood by those skilled in the art that the specific composition can be changed without departing from the idea or purpose of the present disclosure.

図面等において示す各構成の位置、大きさ、形状、範囲などは、実施形態の理解を容易にするため、実際の位置、大きさ、形状、範囲などを表していない場合がある。このため、本開示は、必ずしも、図面等に開示された位置、大きさ、形状、範囲などに限定されない。また、本明細書で引用した刊行物等は、そのまま本明細書の説明の一部を構成する。本明細書において単数形で表される構成要素は、特段文脈で明らかに示されない限り、複数形を含むものとする。なお、本開示において、プラズマ処理とはプラズマエッチングを意味する。シリコン系の基板はプラズマエッチングをされた直後では、親水性を有することが知られている。まず、本開示の親水性保持方法が適用されない場合の、ナノデバイス作製から分子計測までの流れを説明する。 The position, size, shape, range, etc. of each configuration shown in the drawings and the like may not represent the actual position, size, shape, range, etc. in order to facilitate understanding of the embodiment. Therefore, the present disclosure is not necessarily limited to the position, size, shape, range, etc. disclosed in the drawings and the like. In addition, the publications and the like cited in this specification constitute a part of the description of this specification as they are. The components represented in the singular form herein are intended to include the plural, unless explicitly stated in the context. In the present disclosure, plasma processing means plasma etching. It is known that a silicon-based substrate has hydrophilicity immediately after being plasma-etched. First, the flow from nanodevice fabrication to molecular measurement will be described when the hydrophilicity retention method of the present disclosure is not applied.

図1は、ナノデバイスによって分子計測をする際の処理のフローである。ここで、当該フローは、ナノデバイスを計測に利用する検査キットや装置の製品化を想定している。半導体加工技術を利用して検査キットを作製する場合、ウェハー上に薄膜を多数並列して作製(101)した後、それらを個々のセンサ部の単位にダイシングする(102)。 FIG. 1 is a processing flow when measuring molecules with a nanodevice. Here, the flow assumes the commercialization of inspection kits and devices that use nanodevices for measurement. When manufacturing an inspection kit using semiconductor processing technology, a large number of thin films are manufactured in parallel on a wafer (101) and then diced into units of individual sensor units (102).

続いて、溶液槽に組み込む前のウェハーに対して親水化処理(103)を行う。親水化処理は、個々の薄膜を溶液槽に組み込む前にプラズマ処理またはピラニア洗浄を実施することで、効率よく効果的に実施できる。溶液中に含まれる分子の計測を可能にするため、薄膜を別途製造した溶液槽に組み込み、計測チップを作製(104)する。 Subsequently, the wafer before being incorporated into the solution tank is subjected to a hydrophilization treatment (103). The hydrophilization treatment can be carried out efficiently and effectively by performing plasma treatment or piranha cleaning before incorporating each thin film into the solution tank. In order to enable measurement of molecules contained in the solution, a thin film is incorporated into a separately manufactured solution tank to prepare a measurement chip (104).

使用者が計測チップを作製する場合(Case1)、計測チップ作製直後に試料溶液を計測チップに導入(105)し、目的に応じた技術を用いて分子を計測する(106)。使用者とは異なる製造者が計測チップを作製する場合(Case2)、製造段階で使用者の目的に適合した試料溶液を計測チップに添加することは困難であるため、計測チップ作製直後に緩衝溶液を計測チップに導入(107)する。当該計測チップが使用者に渡った後、使用者が計測チップ中の緩衝溶液に計測試料を追加するか、または緩衝溶液を除去した後に試料溶液を計測チップに添加(108)し、その後目的に応じた技術を用いて使用者が分子を計測する(109)。 When the user manufactures the measurement chip (Case 1), the sample solution is introduced into the measurement chip immediately after the measurement chip is manufactured (105), and the molecule is measured using a technique according to the purpose (106). When a manufacturer different from the user manufactures the measurement chip (Case2), it is difficult to add a sample solution suitable for the user's purpose to the measurement chip at the manufacturing stage, so a buffer solution immediately after the measurement chip is manufactured. Is introduced into the measuring chip (107). After the measuring chip is handed over to the user, the user adds the measurement sample to the buffer solution in the measuring chip, or removes the buffer solution and then adds the sample solution to the measuring chip (108), and then for the purpose. The user measures the molecule using the appropriate technique (109).

上記のフローにおいて、使用者が計測チップを作製する場合(Case1)と、使用者とは異なる製造者が計測チップを作製する場合(Case2)と、のどちらの場合であってもナノデバイスを計測に利用する検査キットや装置の製品化には課題があることは既に説明した。本開示の親水性保持方法は、基板表面の親水性の経時的劣化を抑制することによって上記課題を回避可能とする。 In the above flow, the nanodevice is measured regardless of whether the user manufactures the measurement chip (Case1) or the manufacturer different from the user manufactures the measurement chip (Case2). We have already explained that there are problems in commercializing the inspection kits and devices used in the market. The hydrophilicity-retaining method of the present disclosure makes it possible to avoid the above problems by suppressing deterioration of the hydrophilicity of the substrate surface over time.

<実施例1>
図2は、親水化処理が施された基板表面に純水を垂らした際の親水性または撥水性を示す図である。図2に示された基板は、シリコンナイトライド基板(SiN基板)にプラズマ処理によって親水化処理を行ったものである。具体的には、図2に示された基板は、周知の半導体加工技術によって作製される基板であり、CVD(Chemical Vapor Deposition)によって形成されたSiN層をプラズマエッチングして作成したSiN基板である。ここでのSiN基板は、Siを材料とした基板である。親水性の評価は、基板表面に滴下した純水と基板との接触角にて評価した。
<Example 1>
FIG. 2 is a diagram showing hydrophilicity or water repellency when pure water is dropped on the surface of a substrate that has been subjected to a hydrophilic treatment. The substrate shown in FIG. 2 is a silicon nitride substrate (SiN substrate) subjected to hydrophilization treatment by plasma treatment. Specifically, the substrate shown in FIG. 2 is a substrate manufactured by a well-known semiconductor processing technique, and is a SiN substrate produced by plasma etching a SiN layer formed by CVD (Chemical Vapor Deposition). .. The SiN substrate here is a substrate made of Si 3 N 4 as a material. The hydrophilicity was evaluated by the contact angle between the pure water dropped on the surface of the substrate and the substrate.

図2(a)は、プラズマ処理をした直後の基板を用いた場合の実験結果を示す図である。基板表面に滴下した純水は接触角の計測が困難なほど薄く基板上に広がっており、プラズマ処理によってSiN基板は超親水性の状態であったことが確認された。つまり、SiN基板はプラズマエッチングをされた直後には高い親水性を有することを確認した。 FIG. 2A is a diagram showing experimental results when a substrate immediately after plasma treatment is used. It was confirmed that the pure water dropped on the surface of the substrate was so thin that it was difficult to measure the contact angle and spread on the substrate, and that the SiN substrate was in a superhydrophilic state by plasma treatment. That is, it was confirmed that the SiN substrate has high hydrophilicity immediately after being plasma-etched.

図2(b)は、プラズマ処理をしてから3日間経過させた後の基板を用いた場合の実験結果を示す図である。図2(b)に示す例では、本開示の親水性保持方法は適用されていない。SiN基板は、表面にプラズマ処理を施された後、デシケータにて3日間保管され、その後基板表面に純水を滴下して純水の接触角を観察した。純水と基板表面との接触角は約65°と大きく、SiN基板の親水性が短期間で劣化することが確かめられた。つまり、デシケータにて3日間保存しただけでも、シリコン薄膜の表面が導電性の溶液と接触しにくくなるため、ナノポアを形成するための絶縁破壊が生じにくくなる。 FIG. 2B is a diagram showing the experimental results when the substrate is used after 3 days have passed since the plasma treatment. In the example shown in FIG. 2 (b), the hydrophilicity retention method of the present disclosure is not applied. After the surface of the SiN substrate was subjected to plasma treatment, it was stored in a desiccator for 3 days, and then pure water was dropped onto the surface of the substrate and the contact angle of the pure water was observed. The contact angle between pure water and the surface of the substrate was as large as about 65 °, and it was confirmed that the hydrophilicity of the SiN substrate deteriorated in a short period of time. That is, even if the silicon thin film is stored in a desiccator for only 3 days, the surface of the silicon thin film is less likely to come into contact with the conductive solution, so that dielectric breakdown for forming nanopores is less likely to occur.

図2(c)は、本開示の親水性保持方法を適用したSiN基板を用いた場合の実験結果を示す図である。図2(c)に示す例では、基板表面にプラズマ処理をした後、本開示の親水性保護処理方法をSiN基板に適用して基板表面に溶媒で洗い流せる保護層を形成した。その後当該基板をデシケータに3日間保管した後、基板表面に形成された保護層を除去してから純水を基板表面に滴下し、純水の接触角を観察した。 FIG. 2C is a diagram showing experimental results when a SiN substrate to which the hydrophilicity retention method of the present disclosure is applied is used. In the example shown in FIG. 2 (c), after plasma treatment was applied to the surface of the substrate, the hydrophilic protection treatment method of the present disclosure was applied to the SiN substrate to form a protective layer on the surface of the substrate that could be washed away with a solvent. After that, the substrate was stored in a desiccator for 3 days, the protective layer formed on the surface of the substrate was removed, pure water was dropped onto the surface of the substrate, and the contact angle of pure water was observed.

図2(c)の例では、SiN基板の表面に可溶性物質を含む溶液として濃度1MのTris−HCl溶液を滴下し、乾燥させて保護層を形成してSiN基板を保管した。図2(c)に示されているように、親水性保持方法が適用されたSiN基板を用いた場合、基板表面上に滴下した純水は、図2(a)に示されたプラズマ処理直後の観察像とほぼ同様に薄く基板上に広がっている。つまり、本開示の親水性保持方法を適用した基板は、基板表面の超親水性が3日経過した時点においても保持されている。よって、本開示の親水性保持方法を適用したシリコン薄膜は、3日間経過した後でも導電性溶液を接触させ、電圧を印加することによりナノポアを形成できる。なお、図2(c)の例では、純水を基板に垂らす前に溶媒にて保護層を除去している。 In the example of FIG. 2 (c), a Tris-HCl solution having a concentration of 1 M was dropped onto the surface of the SiN substrate as a solution containing a soluble substance, and dried to form a protective layer, and the SiN substrate was stored. As shown in FIG. 2 (c), when a SiN substrate to which the hydrophilicity retention method is applied is used, the pure water dropped on the substrate surface is immediately after the plasma treatment shown in FIG. 2 (a). It spreads thinly on the substrate in almost the same way as the observation image of. That is, the substrate to which the hydrophilicity retaining method of the present disclosure is applied retains the superhydrophilicity of the substrate surface even after 3 days have passed. Therefore, the silicon thin film to which the hydrophilicity retention method of the present disclosure is applied can form nanopores by contacting the conductive solution and applying a voltage even after 3 days have passed. In the example of FIG. 2C, the protective layer is removed with a solvent before the pure water is dropped on the substrate.

図3は、基板表面に垂らした純水の接触角の経時的変化を示す図である。図3中、破線で示された折れ線グラフが本開示の親水性保持処理を実施しなかった場合の接触角を示し、実線で示された折れ線グラフが本開示の親水性保持処理を実施した場合の接触角を示す。上で説明したのと同様、基板の材料はSiであり、基板の保管方法はデシケータ内での保管とした。 FIG. 3 is a diagram showing changes over time in the contact angle of pure water dripping on the surface of the substrate. In FIG. 3, the line graph shown by the broken line shows the contact angle when the hydrophilicity retention treatment of the present disclosure is not performed, and the line graph shown by the solid line shows the hydrophilicity retention treatment of the present disclosure. Indicates the contact angle of. Similarly as described above, the material of the substrate is Si 3 N 4, storage method of the substrate was kept in a desiccator.

親水性保持処理を実施しなかった未処理基板では、プラズマ処理後3日間経過した時点で、純水と基板表面との接触角が60°以上に達し、基板表面の親水性が低下することが見て取れた。一方、本開示の親水性保持処理を行った基板では、プラズマ処理から7日経過後も、純水と基板表面との接触角が10°未満であり、基板表面の親水性が保持されている。 In the untreated substrate that has not been subjected to the hydrophilicity retention treatment, the contact angle between the pure water and the substrate surface reaches 60 ° or more 3 days after the plasma treatment, and the hydrophilicity of the substrate surface may decrease. I could see it. On the other hand, in the substrate subjected to the hydrophilicity retention treatment of the present disclosure, the contact angle between the pure water and the surface of the substrate is less than 10 ° even after 7 days have passed from the plasma treatment, and the hydrophilicity of the surface of the substrate is maintained.

上記のとおり、本開示の親水性保持処理を施したSiN基板の表面は、プラズマ処理をした後7日間経過した後でも、親水性を保持することができる。また、本開示の親水性保持方法は、SiN基板表面の化学的変化を起こさない。言い換えると、Siの一部をOH基に置換するといったSiN基板の物理的および化学的変化を起こさず、SiN基板表面に、溶媒によって除去可能な保護層を形成する。当該保護層は、空気中に含まれる分子等がSiN基板表面に吸着し、SiN基板の親水性が損なわれるのを防ぐことができる。なお、上の説明では、可溶性物質を含む溶液として濃度1MのTris−HCl溶液を用いて保護層を形成したが、保護層の形成にはそれ以外の溶液を用いることもできる。Tris−HCl溶液以外の例については、後に表1にて例示される。また、保護層は、使用する溶液の種類によって、溶媒が乾燥したあと可溶性物質のみが残っている場合もあれば、可溶性物質と非可溶性物質が混在している場合もある。 As described above, the surface of the SiN substrate subjected to the hydrophilicity retaining treatment of the present disclosure can retain the hydrophilicity even after 7 days have passed after the plasma treatment. Further, the hydrophilicity retaining method of the present disclosure does not cause a chemical change on the surface of the SiN substrate. In other words, a protective layer that can be removed by a solvent is formed on the surface of the SiN substrate without causing physical and chemical changes of the SiN substrate such as substituting a part of Si 3 N 4 with an OH group. The protective layer can prevent molecules and the like contained in the air from adsorbing on the surface of the SiN substrate and impairing the hydrophilicity of the SiN substrate. In the above description, the protective layer was formed by using a Tris-HCl solution having a concentration of 1 M as a solution containing a soluble substance, but other solutions can also be used to form the protective layer. Examples other than the Tris-HCl solution are illustrated later in Table 1. Further, depending on the type of solution used, the protective layer may have only soluble substances remaining after the solvent has dried, or may have a mixture of soluble substances and insoluble substances.

<実施例2>
実施例2では、分子の種類および数を電流値にて検出が可能なナノデバイスに対し、実施例1にて説明した親水性保持方法を適用した例について説明する。
<Example 2>
In Example 2, an example in which the hydrophilicity retention method described in Example 1 is applied to a nanodevice capable of detecting the type and number of molecules by a current value will be described.

図4は、ナノデバイス1の構造を示す図である。ナノデバイス1は、上下二つの溶液槽が絶縁性のSiN薄膜11(厚さ2.60nm、材料:Si)によって仕切られた構造である。二つの溶液槽は、それぞれ、シリコン基板12およびポリシリコン13によって囲われる。二つの溶液槽を隔てるSiN薄膜11の幅は、およそ600nm程度であり、一方の溶液槽は、溶液が侵入可能な径150nmの開口を有するカバー14で覆われている。図4には、デバイス構造と併せて、ナノデバイス1の一部を拡大した断面TEM(Transmission Electron Microscope)観察像も示されている。 FIG. 4 is a diagram showing the structure of the nanodevice 1. Nanodevice 1, two upper and lower solution chamber is an insulating SiN film 11 (thickness 2.60Nm, materials: Si 3 N 4) is partitioned structure by. The two solution tanks are surrounded by a silicon substrate 12 and a polysilicon 13, respectively. The width of the SiN thin film 11 that separates the two solution tanks is about 600 nm, and one solution tank is covered with a cover 14 having an opening having a diameter of 150 nm through which the solution can penetrate. FIG. 4 shows an enlarged cross-sectional TEM (Transmission Electron Microscope) observation image of a part of the nanodevice 1 together with the device structure.

既に述べたように、SiN薄膜11には、両溶液槽に導電性溶液を満たした後に、各溶液槽に設置した電極に電圧を印加し、絶縁破壊を生じさせることによって、径が数ナノメートルの細孔(ナノポア)が形成(以下、電圧開口と称する)される。ナノデバイス1の製造方法の詳細については、例えば特許文献WO2016/129111A1に記載された方法を参照することができる。 As described above, the SiN thin film 11 has a diameter of several nanometers by filling both solution tanks with a conductive solution and then applying a voltage to the electrodes installed in each solution tank to cause dielectric breakdown. Pore (nanopore) is formed (hereinafter referred to as voltage opening). For details of the method for manufacturing the nanodevice 1, for example, the method described in Patent Document WO2016 / 129111A1 can be referred to.

ナノデバイス1に電圧開口を実施すると、形成したナノポアを分子が通過する際に発生する電流値の変化を計測することによって核酸等の分子の検出ができることが“Yanagi, I., et al., Fabricating nanopores with diameters of sub-1 nm to 3 nm using multilevel pulse-voltage injection. Sci. Rep., 4(5000) (2014)”において報告されている。 By implementing a voltage opening in nanodevice 1, it is possible to detect molecules such as nucleic acids by measuring changes in the current value generated when molecules pass through the formed nanopores. “Yanagi, I., et al., Fabricating nanopores with diameters of sub-1 nm to 3 nm using multilevel pulse-voltage injection. Sci. Rep., 4 (5000) (2014) ”.

上記電圧開口は、SiN薄膜11に電圧が印加されること、つまりSiN薄膜11が溶液槽に満たした導電性の液体に接していることが要件であるため、本開示の親水性保持方法が見出される以前は電圧開口処理の直前にSiN薄膜11の親水化処理が行われていた。 Since the voltage opening requires that a voltage is applied to the SiN thin film 11, that is, the SiN thin film 11 is in contact with the conductive liquid filled in the solution tank, the hydrophilicity retaining method of the present disclosure has been found. Prior to the voltage opening treatment, the SiN thin film 11 was hydrophilized immediately before the voltage opening treatment.

本開示の親水性保持処理が実施されないナノデバイス1をプラズマ処理後デシケータにて保管し、一日経過した後にSiN薄膜11に対して電圧開口処理を行うと、絶縁破壊が生じない。言い換えると、SiN薄膜11へのナノポアの形成は観察されない。上記デシケータでの保管は一般的な保管方法であり、SiN薄膜11の親水性は、通常の管理方法を適用するとプラズマ処理後一日経過したのみで損なわれてしまうことがわかる。一方、ナノデバイス1が備えるSiN薄膜11に本開示の親水性保持処理を適用すると、デシケータにて一日保管した後でも電圧開口によってナノポアの形成が可能である。 When the nanodevice 1 not subjected to the hydrophilicity retention treatment of the present disclosure is stored in a desiccator after plasma treatment and a voltage opening treatment is performed on the SiN thin film 11 after one day has passed, dielectric breakdown does not occur. In other words, no nanopore formation on the SiN thin film 11 is observed. Storage in the desiccator is a general storage method, and it can be seen that the hydrophilicity of the SiN thin film 11 is impaired only one day after the plasma treatment when a normal management method is applied. On the other hand, when the hydrophilicity retention treatment of the present disclosure is applied to the SiN thin film 11 included in the nanodevice 1, nanopores can be formed by the voltage opening even after being stored in a desiccator for one day.

図5は、本開示の親水性保持処理を適用したナノデバイス1と適用しなかったナノデバイスとでリーク電流を測定した結果を比較した図である。図5において、実線が本開示の親水性保持処理を適用されたナノデバイス1で測定した電流値を示し、破線が本開示の親水性保持処理が適用されなかったナノデバイス1で測定した電流値を示す。 FIG. 5 is a diagram comparing the results of measuring the leak current between the nanodevice 1 to which the hydrophilicity retention treatment of the present disclosure is applied and the nanodevice to which the hydrophilicity retention treatment is not applied. In FIG. 5, the solid line shows the current value measured by the nanodevice 1 to which the hydrophilicity retention treatment of the present disclosure is applied, and the broken line shows the current value measured by the nanodevice 1 to which the hydrophilicity retention treatment of the present disclosure is not applied. Is shown.

電流測定は、上で説明したのと同様、プラズマ処理後、デシケータにて一日保管する条件で実施した。図5に示されているように、親水性保持処理が適用されなかったナノデバイス1では、電極に印加する電圧が10Vに達してもリーク電流の電流値に変化が見られず、電流値がナノポアの形成と見做せる閾値を超えなかった。これは、親水性保持処理が適用されないと撥水のため、導電性溶液がSiN薄膜11に密着せず、電圧を印加してもSiN薄膜11の絶縁破壊が起きないためである。一方、親水性保持処理が適用されたナノデバイス1では、電極に印加する電圧が4Vに達した際に、リーク電流の電流値が離散的に上昇し、SiN薄膜11にナノポアが形成されたことが確認できた。即ち、本開示の親水性保持方法を適用したナノデバイス1では、デシケータにて一日保管した後でも、SiN薄膜11の親水性が保持され、SiN薄膜11に導電性溶液が密着していたことがわかる。 The current measurement was carried out under the condition of storing in a desiccator for one day after plasma treatment as described above. As shown in FIG. 5, in the nanodevice 1 to which the hydrophilicity retention treatment was not applied, no change was observed in the current value of the leak current even when the voltage applied to the electrode reached 10 V, and the current value was changed. The threshold value, which can be regarded as the formation of nanopores, was not exceeded. This is because the conductive solution does not adhere to the SiN thin film 11 due to water repellency unless the hydrophilicity retaining treatment is applied, and dielectric breakdown of the SiN thin film 11 does not occur even if a voltage is applied. On the other hand, in the nanodevice 1 to which the hydrophilicity retention treatment was applied, when the voltage applied to the electrode reached 4 V, the current value of the leak current increased discretely, and nanopores were formed on the SiN thin film 11. Was confirmed. That is, in the nanodevice 1 to which the hydrophilicity retaining method of the present disclosure was applied, the hydrophilicity of the SiN thin film 11 was maintained even after being stored in a desiccator for one day, and the conductive solution was in close contact with the SiN thin film 11. I understand.

図6は、本開示の親水性保持方法を適用したナノデバイス1によって分子計測をする際の処理のフローである。本開示の親水性保持方法の特徴は、図1に示したフローにおける親水化処理(103)の後に、基板表面に可溶性物質を含む溶液を塗布し、塗布した溶液を乾燥して可溶性物質を成分とする保護層を形成する工程(110)が追加されたことにある。また、SiN薄膜11の表面に保護層が形成されているため、使用者とは異なる製造者が計測チップを作製する場合(Case2)であっても、ナノデバイス1に緩衝溶液を導入する工程(107)が不要となる点も特徴である。その他の工程については、図1のフローと同様であるから説明は繰り返さない。 FIG. 6 is a flow of processing when molecular measurement is performed by the nanodevice 1 to which the hydrophilicity retention method of the present disclosure is applied. The feature of the hydrophilicity maintaining method of the present disclosure is that after the hydrophilic treatment (103) in the flow shown in FIG. 1, a solution containing a soluble substance is applied to the surface of the substrate, and the applied solution is dried to contain the soluble substance. The step (110) for forming the protective layer is added. Further, since the protective layer is formed on the surface of the SiN thin film 11, the step of introducing the buffer solution into the nanodevice 1 even when the manufacturer different from the user manufactures the measurement chip (Case 2) (Case 2). Another feature is that 107) is not required. Since the other steps are the same as the flow of FIG. 1, the description will not be repeated.

図7は、ナノデバイス1に形成された保護層15を除去して分子計測を実施する様子が示された図である。保護層15は可溶性物質を成分とするため、溶液槽に溶液を入れる作業と同時に除去することができる。電圧印加回路を保有する溶液槽内に設置されたナノデバイス上の保護層15を溶液槽への溶液充填によってSiN薄膜11の表面から除去した後に、電圧開口によりナノポアを形成する。その後に、例えばDNAのような分子の分子計測が行われる。 FIG. 7 is a diagram showing a state in which the protective layer 15 formed on the nanodevice 1 is removed and molecular measurement is performed. Since the protective layer 15 contains a soluble substance as a component, it can be removed at the same time as the operation of putting the solution in the solution tank. After removing the protective layer 15 on the nanodevice installed in the solution tank having the voltage application circuit from the surface of the SiN thin film 11 by filling the solution tank with the solution, nanopores are formed by the voltage opening. After that, molecular measurement of a molecule such as DNA is performed.

図8は、本開示の親水性保持方法を適用したナノデバイス1で観察された電圧印加累積時間とイオン電流との関係を示す図である。印加する電圧は、上記文献“Yanagi, I., et al.”に記されたパルス状電圧であり、1.0−10A以上の電流が流れると、ナノポア形成を示す絶縁破壊が起きたことを示す。図8は、実施例2に記載のナノデバイス1の例では、2.0×10−10Aが流れるナノポアを形成できることが確認できた。 FIG. 8 is a diagram showing the relationship between the cumulative voltage application time and the ionic current observed in the nanodevice 1 to which the hydrophilicity retention method of the present disclosure is applied. The applied voltage is the pulsed voltage described in the above-mentioned document "Yanagi, I., et al.", And when a current of 1.0-10 A or more flows, dielectric breakdown indicating nanopore formation occurs. Is shown. In FIG. 8, it was confirmed that in the example of nanodevice 1 described in Example 2, nanopores in which 2.0 × 10-10 A flows can be formed.

図9は、ナノデバイス1の初期欠陥の有無を示す図である。具体的には、図9には、本開示の親水性保持方法が適用されたナノデバイス1を長期保管した際の特性評価結果が示されている。上述したように、実施例2に係るナノデバイス1では、電圧開口を行う前であっても10−10A以上の電流が流れる場合、力学的な応力変化による破壊等により初期欠陥が生じたことを意味する。図9に示されているように、本開示の親水性保持方法が適用されたナノデバイス1は、3ヶ月以上長期保管を行っても電圧開口の実施前のリーク電流が10−10A未満であり、初期欠陥が生じていない。即ち、本開示の親水性保持方法は、シリコン薄膜に力学的な負荷を与えずに親水性を保持することができる。 FIG. 9 is a diagram showing the presence or absence of initial defects in the nanodevice 1. Specifically, FIG. 9 shows the characteristic evaluation results when the nanodevice 1 to which the hydrophilicity retention method of the present disclosure is applied is stored for a long period of time. As described above, in the nanodevice 1 according to the second embodiment, when a current of 10-10 A or more flows even before the voltage opening, an initial defect occurs due to fracture due to a mechanical stress change or the like. Means. As shown in FIG. 9, the nanodevice 1 to which the hydrophilicity retention method of the present disclosure is applied has a leakage current of less than 10-10 A before the voltage opening even after long-term storage for 3 months or more. Yes, no initial defects have occurred. That is, the hydrophilicity-retaining method of the present disclosure can maintain the hydrophilicity without applying a mechanical load to the silicon thin film.

図10は、ナノデバイス1の初期欠陥の有無を示す更なる図である。図10には、ナノデバイス1を保管してから経過した日数と絶縁破壊電圧との関係が示されている。図10に示されているように、本開示の親水性保持方法が適用されたナノデバイス1の絶縁破壊電圧は3ヶ月以上長期保管を行ってもおよそ4V程度であり、変化しないことを確認した。したがって、本開示の親水性保持方法はナノデバイス1の特性を劣化することなくナノデバイス1の親水性を保持することが可能である。つまり、本開示の親水性保持方法が適用されたナノデバイス1は分子計測の精度を低下させない。 FIG. 10 is a further diagram showing the presence or absence of initial defects in the nanodevice 1. FIG. 10 shows the relationship between the number of days elapsed since the nanodevice 1 was stored and the dielectric breakdown voltage. As shown in FIG. 10, it was confirmed that the dielectric breakdown voltage of the nanodevice 1 to which the hydrophilicity retention method of the present disclosure was applied was about 4 V even after long-term storage for 3 months or longer, and did not change. .. Therefore, the hydrophilicity-retaining method of the present disclosure can maintain the hydrophilicity of the nanodevice 1 without deteriorating the characteristics of the nanodevice 1. That is, the nanodevice 1 to which the hydrophilicity retention method of the present disclosure is applied does not reduce the accuracy of molecular measurement.

図11は、分子計測の測定結果の例を示す図である。本開示の親水性保持方法が適用されたナノデバイス1において、電圧開口によってナノポアを形成した場合、安定したベースライン電流を計測できた(図11(a))。このナノポアが形成されたナノデバイスを用いて典型的な生体分子である一本鎖DNA分子を計測したところ、DNA分子が通過することにより抵抗値が増加して電流値が減少する様子が安定して観測された(図11(b))。 FIG. 11 is a diagram showing an example of measurement results of molecular measurement. In the nanodevice 1 to which the hydrophilicity retention method of the present disclosure was applied, when nanopores were formed by a voltage aperture, a stable baseline current could be measured (FIG. 11 (a)). When a single-stranded DNA molecule, which is a typical biomolecule, was measured using the nanodevice in which this nanopore was formed, it was stable that the resistance value increased and the current value decreased as the DNA molecule passed. Was observed (Fig. 11 (b)).

上の実施例1および2では、SiN薄膜11の表面に保護層15を形成するのに、濃度1MのTris−HCl溶液を利用した。保護層15の形成には、上記以外の可溶性物質を含んだ溶液を利用することもできる。表1に様々な条件で本開示の親水性保持方法を適用したナノデバイスの電圧開口の実験結果を示した。 In Examples 1 and 2 above, a Tris-HCl solution having a concentration of 1 M was used to form the protective layer 15 on the surface of the SiN thin film 11. A solution containing a soluble substance other than the above can also be used for forming the protective layer 15. Table 1 shows the experimental results of the voltage opening of the nanodevice to which the hydrophilicity retention method of the present disclosure is applied under various conditions.

Figure 0006975609
Figure 0006975609

表1には、保護層15を形成するのに用いた溶液に含まれる溶質(可溶性物質)の種類、保護層15を形成して常温常圧の解放空間で保管してからの経過時間(h)、上記経過時間(h)を日数単位に換算した経過日数(d)、電圧開口を実施する前に計測した初期電流値(A)およびナノポア形成の基準となる絶縁破壊電圧(V)が項目として含まれる。 Table 1 shows the types of solutes (soluble substances) contained in the solution used to form the protective layer 15, and the elapsed time (h) after the protective layer 15 was formed and stored in an open space at normal temperature and pressure. ), The elapsed days (d) obtained by converting the elapsed time (h) into days, the initial current value (A) measured before the voltage opening is performed, and the breakdown voltage (V) which is the reference for nanopore formation. Included as.

保護層15を形成するのに用いた溶液としては、Tris−HCl緩衝液およびHEPES緩衝液並びにそれら緩衝液に塩化カリウム、塩化セシウムまたは塩化リチウムを添加した溶液を用い、それらを種々の濃度で調整した。 As the solution used to form the protective layer 15, Tris-HCl buffer and HEPES buffer, and a solution obtained by adding potassium chloride, cesium chloride or lithium chloride to these buffers were used, and they were adjusted at various concentrations. bottom.

濃度および含まれる可溶性物質の種類が異なる複数の溶液で、ナノポア形成を示す絶縁破壊電圧が観察された。上で説明したとおり、絶縁破壊電圧は上下の溶液槽を隔てる絶縁性のSiN薄膜11に対して電圧を印加することによって細孔が形成される時点の電圧値である。絶縁破壊電圧の電圧値の観察は、上下二つの溶液槽に通電が発生したことを示す。本試験の結果から本開示の親水性保持方法を適用することによって、ナノデバイス1を長期間常温、常圧下で親水性を保って保管可能であることが示された。 Breakdown voltages indicating nanopore formation were observed in multiple solutions with different concentrations and types of soluble materials. As described above, the dielectric breakdown voltage is a voltage value at the time when pores are formed by applying a voltage to the insulating SiN thin film 11 that separates the upper and lower solution tanks. Observation of the voltage value of the dielectric breakdown voltage indicates that energization has occurred in the upper and lower solution tanks. From the results of this test, it was shown that by applying the hydrophilicity retention method of the present disclosure, the nanodevice 1 can be stored for a long period of time at room temperature and under normal pressure while maintaining hydrophilicity.

なお、表1に記載されているとおり、濃度が1MのTris−HCl緩衝液を基板に塗布し、90日間常温常圧にて保管した場合に、電圧開口が実施される前の時点で絶縁性が失われる初期破壊現象の発生事例が観察された。 As shown in Table 1, when a Tris-HCl buffer having a concentration of 1 M is applied to the substrate and stored at normal temperature and pressure for 90 days, the insulating property is before the voltage opening is performed. An example of the initial destruction phenomenon was observed.

基板の初期破壊現象は、溶液の乾燥処理によって形成された基板表面の可溶性物質の結晶が、基板の構造を破壊したため生じたと推察される。より具体的には、可溶性物質を含む溶液が乾燥する過程で保護層が収縮し、基板に生じた応力が基板の構造を破壊したと考えられる。上記応力は、保護層の形成に用いる溶液の濃度が高いほど大きくなる傾向がある。それ故、本開示の親水性保持方法は、当該方法を適用するデバイスの構造に応じて適切な濃度の溶液を選択して保護層を形成することが望ましい。また、先に述べた物質計測への影響軽減の観点からも保護層形成のために塗布する溶液の濃度は適宜調整することが望ましい。 It is presumed that the initial fracture phenomenon of the substrate was caused by the crystals of the soluble substance on the surface of the substrate formed by the drying treatment of the solution, which destroyed the structure of the substrate. More specifically, it is considered that the protective layer contracted in the process of drying the solution containing the soluble substance, and the stress generated on the substrate destroyed the structure of the substrate. The stress tends to increase as the concentration of the solution used to form the protective layer increases. Therefore, in the hydrophilicity retention method of the present disclosure, it is desirable to select a solution having an appropriate concentration according to the structure of the device to which the method is applied to form a protective layer. Further, from the viewpoint of reducing the influence on the substance measurement described above, it is desirable to appropriately adjust the concentration of the solution to be applied for forming the protective layer.

保護層を形成するために用いる溶液の濃度の最適範囲は、本開示の親水性保持方法を適用するナノデバイスの構造、基板の材質、計測対象物質および計測方法に応じて調節される。ナノデバイスの構造や基板の材質、計測対象物質、計測方法が固定の条件であれば、本開示の親水性保持方法に用いる可溶性物質の種類や溶液の濃度は、分子計測の経験者であれば容易に設計できる。 The optimum range of the concentration of the solution used to form the protective layer is adjusted according to the structure of the nanodevice to which the hydrophilicity retention method of the present disclosure is applied, the material of the substrate, the substance to be measured, and the measurement method. If the structure of the nanodevice, the material of the substrate, the substance to be measured, and the measurement method are fixed conditions, the type of soluble substance and the concentration of the solution used in the hydrophilicity retention method of the present disclosure can be determined by those who have experience in molecular measurement. Easy to design.

[分子計測への影響]
次に本開示の親水性保持方法が分子計測に与える影響について説明する。本開示では、プラズマ処理がなされた基板に溶解性の物質を含む溶液を塗布して乾燥させるため、基板表面には溶解していた可溶性物質が残存する。つまり、本開示の親水性保持方法を適用した計測ユニットに計測溶液を添加した場合、計測溶液中に可溶性物質が溶解して混合することとなる。
[Impact on molecular measurement]
Next, the effect of the hydrophilicity retention method of the present disclosure on molecular measurement will be described. In the present disclosure, since the solution containing the soluble substance is applied to the plasma-treated substrate and dried, the dissolved soluble substance remains on the surface of the substrate. That is, when the measurement solution is added to the measurement unit to which the hydrophilicity retention method of the present disclosure is applied, the soluble substance is dissolved and mixed in the measurement solution.

しかしながら、一般に溶液中の分子を計測する場合、溶液の溶媒は緩衝液または塩を含む緩衝液であるため、計測時に使用する緩衝液に含まれる溶質と同一の可溶性物質を保護層の形成に利用することによって、保護層の計測溶液への混入が計測に与える影響を軽減することができる。 However, when measuring molecules in a solution, since the solvent of the solution is a buffer solution or a buffer solution containing a salt, the same soluble substance as the solute contained in the buffer solution used at the time of measurement is generally used for forming the protective layer. By doing so, it is possible to reduce the influence of the protective layer in the measurement solution on the measurement.

[まとめ]
本開示の親水性保持方法の特徴は、プラズマ処理後に基板に塗布する溶液に含まれる物質が可溶性であることである。可溶性の物質が溶解した溶液を基板表面に塗布し、その後乾燥することによって、基板表面に可溶性の保護層が形成されて基板表面が保護される。つまり、本開示の親水性保持方法を適用することによって空気中に存在する分子などが基板表面に直接吸着することを防ぐことができる。
[summary]
The feature of the hydrophilicity retention method of the present disclosure is that the substance contained in the solution applied to the substrate after the plasma treatment is soluble. By applying a solution in which a soluble substance is dissolved to the surface of the substrate and then drying, a soluble protective layer is formed on the surface of the substrate to protect the surface of the substrate. That is, by applying the hydrophilicity retaining method of the present disclosure, it is possible to prevent molecules and the like existing in the air from being directly adsorbed on the surface of the substrate.

また、保護層が可溶性であることから、後に溶液を添加することによって容易に基板表面から保護層を除去できる。なお、可溶性物質の種類には特段の制限はないが、表1に記載された塩化リチウムの試験では塩化リチウムの潮解性により乾燥処理後の保管期間中に基板表面に水滴が付着する例が観察された。この結果から保管の簡易性や安定性を考慮すると、可溶性物質には潮解性のない物質を選択することが望ましい。 Further, since the protective layer is soluble, the protective layer can be easily removed from the surface of the substrate by adding a solution later. Although there are no particular restrictions on the type of soluble substance, in the lithium chloride test shown in Table 1, it was observed that water droplets adhered to the substrate surface during the storage period after the drying treatment due to the deliquescent property of lithium chloride. Was done. From this result, considering the ease of storage and stability, it is desirable to select a non-deliquescent substance as the soluble substance.

本開示の親水性保持効果を好適に発揮するためには、可溶性物質が基板表面上に未塗布部分がないように塗布されることが望ましい。例えば、結晶性物質は溶媒の乾燥時に再結晶化が行われ、未塗布部分が発生する可能性がある。一方、非結晶性の可溶性物質を保護層形成に用いた場合、溶媒乾燥時に基板表面にアモルファス状の保護層が形成される。そのため、非結晶性の可溶性物質を用いると、基板表面に未塗布部分を生じることなく保護層を安定的に形成できる。したがって、本開示の親水性保持効果を好適に活かすためには、可溶性かつ非結晶性の物質を基板表面に塗布することが好ましい。 In order to suitably exert the hydrophilicity retaining effect of the present disclosure, it is desirable that the soluble substance is applied so that there is no unapplied portion on the surface of the substrate. For example, the crystalline material may be recrystallized when the solvent dries, resulting in uncoated portions. On the other hand, when a non-crystalline soluble substance is used for forming the protective layer, an amorphous protective layer is formed on the surface of the substrate when the solvent is dried. Therefore, when a non-crystalline soluble substance is used, the protective layer can be stably formed without forming an uncoated portion on the surface of the substrate. Therefore, in order to suitably utilize the hydrophilicity retaining effect of the present disclosure, it is preferable to apply a soluble and amorphous substance to the surface of the substrate.

なお、本発明は上記した実施例に限定されるものではなく、様々な変形例が含まれる。例えば、上記した実施例は本発明を分かりやすく説明するために詳細に説明したものであり、必ずしも説明した全ての構成を備えるものに限定されるものではない。また、ある実施例の構成の一部を他の実施例の構成に置き換えることが可能であり、また、ある実施例の構成に他の実施例の構成を加えることも可能である。また、各実施例の構成の一部について、他の構成の追加・削除・置換をすることが可能である。 The present invention is not limited to the above-described embodiment, and includes various modifications. For example, the above-described embodiment has been described in detail in order to explain the present invention in an easy-to-understand manner, and is not necessarily limited to the one including all the described configurations. Further, it is possible to replace a part of the configuration of one embodiment with the configuration of another embodiment, and it is also possible to add the configuration of another embodiment to the configuration of one embodiment. Further, it is possible to add / delete / replace a part of the configuration of each embodiment with another configuration.

上述したように、本開示の親水性保持方法を適用することにより、親水性の面を有する親水性部材と、上記面上に形成された、可溶性物質を含む保護層と、を有する部材を作製することができる。当該部材は、例えば、溶液中に含まれるDNA分子を計測するナノデバイスに用いることができる。さらに、本開示の親水性保持方法は、ナノデバイス以外にも、親水性の表面を有する部材全般に適用することができる。 As described above, by applying the hydrophilicity retaining method of the present disclosure, a member having a hydrophilic member having a hydrophilic surface and a protective layer containing a soluble substance formed on the surface is produced. can do. The member can be used, for example, in a nanodevice for measuring DNA molecules contained in a solution. Further, the hydrophilicity retaining method of the present disclosure can be applied to all members having a hydrophilic surface, in addition to nanodevices.

1…ナノデバイス
11…SiN薄膜
12…シリコン基板
13…ポリシリコン
14…カバー
15…保護層
1 ... Nanodevice 11 ... SiN thin film 12 ... Silicon substrate 13 ... Polysilicon 14 ... Cover 15 ... Protective layer

Claims (9)

親水性の面を有する親水性部材と、
前記面上に形成された、緩衝液中の溶質である可溶性物質を含む保護層と、
を有し、
前記保護層は緩衝液によって前記親水性部材の前記面から洗浄除去可能である親水性保持基材。
A hydrophilic member with a hydrophilic surface,
A protective layer containing a soluble substance, which is a solute in the buffer solution , formed on the surface thereof.
Have,
The protective layer is a hydrophilic retention base material that can be washed and removed from the surface of the hydrophilic member by a buffer solution.
前記親水性部材はシリコンを材料に含む、
請求項1に記載の親水性保持基材。
The hydrophilic member contains silicon as a material.
The hydrophilic retention base material according to claim 1.
前記可溶性物質として非結晶性の物質を含む、
請求項1に記載の親水性保持基材。
A non-crystalline substance is included as the soluble substance,
The hydrophilic retention base material according to claim 1.
請求項1に記載の親水性保持基材を含む計測装置。 A measuring device including the hydrophilicity-retaining substrate according to claim 1. 請求項1に記載の親水性保持基材を有するデバイスであって、
前記親水性部材は、厚さが1μm以下の薄膜形状かつ絶縁性であり、
前記親水性部材が有する二面のうち少なくとも一方の表面に前記可溶性物質を含む保護層が形成されているデバイス。
A device having the hydrophilicity-retaining substrate according to claim 1.
The hydrophilic member has a thin film shape with a thickness of 1 μm or less and is insulating.
A device in which a protective layer containing the soluble substance is formed on at least one of the two surfaces of the hydrophilic member.
前記親水性部材を挟んで両側に二つの溶液槽が設けられている、
請求項5に記載のデバイス。
Two solution tanks are provided on both sides of the hydrophilic member.
The device according to claim 5.
前記溶液槽には電極が設けられている、
請求項6に記載のデバイス。
The solution tank is provided with electrodes.
The device according to claim 6.
基板表面を親水化処理する工程と、
親水化処理後の前記基板表面に可溶性物質を含む緩衝液を塗布する工程と、
塗布した前記緩衝液を乾燥させ、前記可溶性物質を含む保護層を形成する工程と、
を有し、
前記保護層は緩衝液によって前記親水化処理後の前記基板表面から洗浄除去可能である基板表面の親水性保持方法。
The process of hydrophilizing the surface of the substrate and
A step of applying a buffer solution containing a soluble substance to the surface of the substrate after the hydrophilization treatment, and
The step of drying the applied buffer solution to form a protective layer containing the soluble substance, and
Have,
A method for maintaining hydrophilicity on a substrate surface, wherein the protective layer can be washed and removed from the surface of the substrate after the hydrophilic treatment with a buffer solution.
前記基板はシリコンを材料に含む、
請求項8に記載の親水性保持方法。
The substrate contains silicon as a material,
The method for maintaining hydrophilicity according to claim 8.
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